tbuckley/cabot-search huggingface dataset:
Pembrolizumab (pembro) plus mFOLFOX7 or FOLFIRI for metastatic colorectal cancer (CRC) in KEYNOTE-651: Long-term follow-up of cohorts B and D.
Authors: Richard D. Kim, Mustapha Tehfe, Petr Kavan, Jorge Chaves, Jeremy S. Kortmansky, Eric Xueyu Chen, Christopher Hanyoung Lieu, Lucas Wong, Marwan Fakih, Kristen Renee Spencer, Qing Zhao, Raluca Predoiu, Chenxiang Li, David Carpenter, Pierre Leconte, E. Gabriela Chiorean
Journal: Journal of Clinical Oncology (2022)

3521 Background: Response to antiPD-1 monotherapy is poor in patients (pts) with advanced microsatellite stable (MSS)/mismatch-repair proficient (pMMR) CRC. Combination of chemotherapy with antiPD-1 pembro may potentiate the antitumor immune response and provide greater antitumor activity than either agent alone. Combination of pembro and mFOLFOX7 or FOLFIRI in the ongoing phase 1b multicohort KEYNOTE-651 (NCT03374254) study in metastatic MSS/pMMR CRC showed antitumor activity. We present results with approximately 20 mo of additional follow-up. Methods: Pts had metastatic MSS/pMMR CRC and were previously untreated (cohort B) or received 1 prior line including a fluoropyrimidine + oxaliplatin (cohort D). Pts received pembro 200 mg Q3W + mFOLFOX7 Q2W (cohort B) or pembro 200 mg Q3W + FOLFIRI Q2W (cohort D). Primary end points were safety (DLT) and RP2D. Secondary end point was ORR per RECIST v1.1 by investigator review. DOR, DCR, and PFS per RECIST v1.1, and OS were exploratory end points. Results: Median study follow-up (range) at data cutoff (Oct 15, 2021) was 30.2 mo (25.0-43.6) for cohort B (n = 31) and 33.5 mo (25.2-43.2) for cohort D (n = 32). Treatment was discontinued in 29 pts (94%) in cohort B and 28 pts (88%) in cohort D, mostly because of PD (61% and 66%, respectively). At prior analysis (Feb 10, 2020), RP2D was confirmed as the starting dose in both cohorts; no new DLT had occurred. In cohort B, gr 3/4 TRAEs occurred in 18 pts (58%), most commonly neutropenia and decreased neutrophil count (both n = 5; 16%); 19 pts (61%) discontinued drug because of a TRAE. In cohort D, gr 3/4 TRAEs occurred in 17 pts (53%), most commonly, neutropenia (n = 7; 22%), diarrhea and fatigue (both n = 4; 13%); 3 pts (9%) discontinued drug because of a TRAE. There were no gr 5 TRAEs in either cohort. Efficacy by cohort and KRAS mutation status are below (Table). PD-L1 data and DNA/RNA-based biomarker data including GEP, consensus signatures, TMB, and LoF mutations will be included in the presentation. Conclusions: After 2.5 y of follow-up, the combination of pembro with either mFOLFOX7 or FOLFIRI continued to demonstrate a manageable safety profile with no new safety signals. Efficacy data from these single-arm cohorts appear comparable to historical data for current SOC. Clinical trial information: NCT03374254. [Table: see text]
Antibodies and cell immunity after vaccination with tozinameran (BNT162b2) in workers of National Comprehensive Cancer Center (NCCC) in Slovakia.
Authors: Patrik Palacka, Monika Polanova, Alena Svobodova, Jan Zigmond, Katarina Zanchetta, Vlasta Gombarova, Martina Vulganova, Jan Slopovsky, Jana Obertova, Michal Mego, Lubos Drgona, Juraj Pechan
Journal: Journal of Clinical Oncology (2022)

e18774 Background: Vaccination remains the leading strategy against Covid-19 worldwide. BNT 162b2 (tozinameran) belongs among first licensed vaccines with good efficacy. However, the role of monitoring both, antibodies and cell immunity after vaccination remains unclear. Methods: We conducted a 6-month prospective study involving vaccinated workers of NCCC in Slovakia who were tested for the presence of neutralizing antibodies and cell immunity after second dose of tozinameran. SARS-CoV-2 IgG antibodies were detected by the Atellica IM sCOVG, a fully automated 2-step sandwich immunoassay using indirect chemiluminescent technology. Blood samples were tested by two IGRA tests (Quantiferon RUO and CoviFeron) to assess interferon-γ (IFN-γ) responses to SARS CoV-2 spike protein antigen and nucleocapsid protein antigen. Results were stratified by gender and body mass index. P values for categorical variables were calculated using χ 2 or Fishers exact test. P values for continuous variables were calculated using T test and Wilcoxon-Mann-Whitney test. Value of statistical significance was set to 0.05. Data were analyzed using SAS 9.4 software. Results: Medical records of 94 respondents (71 females) were analyzed. Mean age was 40.2 years (23 – 62 years) and mean body mass index (BMI) ± standard error of mean (SEM) was 26.4±2.7 (21.3 – 31.7). Twenty-two (23.4 %) respondents had Covid-19 before first, 5 (5.3 %) before second, and 2 (2.15 %) after second dose of vaccine (P &lt; 0.0001). IgG were tested 24.4±5.0, 50.2±12.1, and 187.9±12.8 days after second vaccination. IgG index progressively decline with corresponding values 126.81±40.34, 93.55±51.29, and 17.68±29.07 (P &lt; 0.0001). Mean time from second vaccination to cell immunity testing was 157.2±101.3 days. Forty-eight (51.1 %) of respondents had negative, 6 (6.4 %) border line, and 40 (42.6 %) positive cell immunity (P &lt; 0.0001). Conclusions: Our study confirmed the efficacy of tozinameran despite both, rapid decline of antibodies and absence of cell immunity in majority of subjects.
Study of antitumor activity of 2-quinoline-2-yl-derivative 1,3-tropolone in PDX models of lung cancer.
Authors: Ekaterina A. Lukbanova, Elena A. Dzhenkova, Ekaterina Fedorovna Komarova, Marina A. Engibaryan, Viktoriya L. Volkova, Mamuka V. Bauzhadze, Yulia V. Ulianova, Irina V. Pustovaya, Elena G. Goncharova, Mary L. Maldonado, Natalia A. Chertova, Maria A. Cherkes, Astanda K. Gvaramiya, D. V. Khodakova, Nataliya Shevchenko, Anna S. Goncharova
Journal: Journal of Clinical Oncology (2022)

e20523 Background: The purpose of the study was to reveal the antitumor effect of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in subcutaneous PDX models of human non-small cell lung cancer (NSCLC). Methods: The studied tropolone was synthesized using a method of expanding the o-quinone cycle. Acute tropolone toxicity was evaluated by the survival and changes in the health status of female Balb/c Nude mice. Antitumor tropolone effects were studied in subcutaneous patient-derived xenograft (PDX) models of human squamous cell lung cancer in Balb/c Nude mice. The average volumes of tumor nodes and tumor growth inhibition (TGI%) rate were taken into account. Biochemical blood tests and histological analysis of the tumor material were performed in recipient mice. Results: An analysis of acute tropolone toxicity did not reveal the lethal dose. The maximal TGI, 73.5% for females and 74.4% for males, was observed on day 36 of the experiment in group 5 which received 2.75 mg/g tropolone. The average tumor volumes in females of this group were 431.3 mm 3 on day 33 of the experiment, in males – 428.9 mm 3 on day 30, and then the tumor volumes declined. Biochemical blood tests and histological analysis of the tumor material in recipient mice confirmed the tendency demonstrated during the analysis of the TGI dynamics, which in turn was the result of the dose-dependent antitumor effect of the studied tropolone. Conclusions: The research demonstrated the antitumor activity of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone against subcutaneous PDX models of human NSCLC. The revealed tendencies can be used to search for effective modes of the compound application in clinical practice.
The value of a negative genetic result when triaging an adnexal mass.
Authors: Yitzhack Asulin, Charles J. Dunton, Victoria Haverbusch, James Done, Rowan Bullock, Daniel Ure, Marisa Debboli-Cop, Jessica Greenwood, Lesley Northrop
Journal: Journal of Clinical Oncology (2022)

e17553 Background: The baseline risk for ovarian cancer in the general population is 1.2% 1 . However, women with germline variants in ovarian cancer-associated genes can have a much higher baseline risk for ovarian cancer, up to 54% 2 . Such a difference in baseline risk presents a triaging challenging for physicians when evaluating adnexal masses. It is well known that identifying pathogenic variants in hereditary cancer syndrome genes often leads to changes in care. Less is known about the utility of negative genetic testing results, specifically in the context of adnexal mass assessment. Methods: An observational, prospective study was designed to examine the clinical impact of multivariate index assay (MIA) and germline genetic testing in patients with a known adnexal mass planned for surgery. Inclusion criteria were: female subjects aged 18-65, presence of an adnexal mass, receiving MIA, and consideration of germline genetic testing. Enrolled physicians selected patients under their care that met inclusion criteria and filled out a short survey describing how the results of each test impacted clinical management. This study was considered IRB-exempt as all information was de-identified. Results: 23 patients were enrolled that received both MIA and germline genetic testing. 21 cases had negative genetic testing and two had positive genetic testing. Both patients with positive genetic testing had low-risk MIA results. Both had risk-reduction surgery with benign findings. Three patients had high-risk MIA results with negative genetic results. All patients had a serial monitoring plan of care. Nine patients with low-risk MIA results and negative genetic results proceeded to surgery. No malignancies were reported. Of the 21 patients with negative genetic results, 17 were not immediately planned for surgery. Conclusions: While not reaching statistical significance, there is a strong association between a negative genetic result and non-immediate surgical intervention. While positive genetic testing results may lead to more aggressive, prophylactic surgical management, negative genetic results may support an expectant management approach. Effectively ruling out the most common hereditary cancer predisposition syndromes may provide physicians with useful insight into a patient's baseline risk. [Table: see text]
Hepatic artery infusion chemotherapy (HAIC) combined with apatinib and camrelizumab for hepatocellular carcinoma (HCC) in BCLC stage c: A prospective, single-arm, phase II trial (TRIPLET study).
Authors: Yang-Kui Gu, Tian-Qi Zhang, Meng-Xuan Zuo, Zhi-Jun Geng, Ji-Bin Li, Zi-Lin Huang, Pei-Hong Wu
Journal: Journal of Clinical Oncology (2022)

4106 Background: The combination of anti-angiogenesis and immune checkpoint blockade has been proven to improve clinical outcomes of advanced HCC. We assessed the efficacy and safety of HAIC combined with apatinib and camrelizumab for BCLC stage C HCC. Methods: Consecutive treatment-naive patients with BCLC stage C HCC were enrolled in this phase II trial (NCT04191889). Eligible patients were administrated with HAIC (oxaliplatin 85 mg/m 2 , leucovorin 400 mg/m 2 and fluorouracil 2500 mg/m 2 ; q3w), combined with apatinib (250 mg qd) and camrelizumab (200 mg q3w) for 6 cycles, followed by maintenance therapy with apatinib and camrelizumab until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Following an optimal Simon 2-stage design, 26 eligible patients needed to be included in the first stage, of whom at least 11 patients had to achieve objective responses to warrant further investigation in the second stage. Results: In the first stage, confirmed ORR was achieved in 16 and 20 patients per RECIST v1.1 and mRECIST, respectively, therefore enrollment of the second stage continued. From 4/13/2020 to 1/31/2022, 31 eligible patients were enrolled and 29 evaluable for efficacy analyses. The 31 patients were characterized with median age 45 years (range 30-67), men 96.77%, Child-Pugh A 100%, portal vein tumor thrombus Vp 1-2/Vp 3-4 25.81%/45.16%, and extrahepatic metastasis 12.90%. As of 1/31/2022, with a median follow-up of 18.07 months (95% CI 14.10 to 22.04), the confirmed ORR was 70.96% (95% CI, 53.41%-83.91%) with 22 partial responses (PR) per RECIST v1.1,while 87.10% (95% CI, 71.15%-94.87%) with 3 (9.68%) complete responses (CR) and 24 (77.42%) PR per mRECIST. The disease control rate (DCR) was 87.10% (95% CI, 71.15%-94.87%) whether per RECIST v1.1 or mRECIST. The median time to response (TTR) was 2.67 months (interquartile range (IQR), 1.43-2.96) per RECIST v1.1 and 2.03 months (IQR, 1.37-2.80) per mRECIST. The median progression-free survival (PFS) time was 9.37 months (95% CI 7.00 to 11.73) per RECIST v1.1 and 9.63 months (95% CI 5.82 to 13.44) per mRECIST, in particular, the liver-specific median PFS time was 10.80 months (95% CI 5.88 to 15.72) per mRECIST. The 6-month, 12-month, and 18-month overall survival rate were 93.1%, 85.8%, and 65.8%, respectively. Grade ≥3 adverse events (AEs) occurred in 74.19% of the patients, of which the most common AEs were decreased neutrophils (52.17%), decreased lymphocytes (43.38%), and increased ALT and AST (30.43% and 43.48% for each). Conclusions: The triplet treatment of HAIC, apatinib and camrelizumab showed promising clinical benefits and acceptable safety for BCLC Stage C HCC. Further confirmatory randomized controlled trial is about to get underway. Clinical trial information: NCT04191889.
Defining “platinum-ineligible” patients with metastatic urothelial cancer (mUC).
Authors: Shilpa Gupta, Joaquim Bellmunt, Elizabeth R. Plimack, Guru P. Sonpavde, Petros Grivas, Andrea B. Apolo, Sumanta K. Pal, Arlene O. Siefker-Radtke, Thomas W. Flaig, Matt D. Galsky, Jonathan E. Rosenberg
Journal: Journal of Clinical Oncology (2022)

4577 Background: Treatment (tx) landscape has evolved significantly for cisplatin-ineligible mUC patients (pts). Carboplatin and gemcitabine followed by avelumab (Av) maintenance is the current preferred standard. Although pembrolizumab (P) and atezolizumab (At) were approved as 1L therapy for these pts in 2017, the FDA has now restricted the use of 1L P to “platinum ineligible” mUC pts. We previously suggested a consensus definition for “platinum-ineligible” pts with mUC (Gupta et al. ASCO GU 2019). We now updated the consensus definition for standard therapy and clinical trial eligibility in the current tx era. Methods: We surveyed 60 genitourinary medical oncologists in the US (similar cohort to 2019) using an online tool consisting of several clinical parameters used in our initial survey with additional questions related to current available tx options. Different age and creatinine thresholds in combination with ECOG PS along with other clinically relevant established criteria were analyzed. We compiled the responses to generate a consensus definition. Results: All 60 respondents provided 100% responses. Respondents (94%) reported using a carboplatin-based regimen followed by Av and 6% reported using carboplatin-based regimen followed by P for cisplatin-ineligible mUC pts. 17/60 (28.3%) and 29/60 (48.3%) checked PD-L1 status prior to using P or At respectively. Survey results for the most common responses are presented in the Table. Conclusions: Based on the survey, any mUC pt meeting one the following 5 parameters should be considered "platinum-ineligible”: ECOG PS &gt; / = 3; Cr Cl &lt; 30 ml/min; peripheral neuropathy &gt; / =Grade 2; NYHA Heart Failure Class &gt; 3; ECOG PS 2 AND Cr Cl &lt; 30 ml/min. These criteria are proposed to guide treatment recommendations and standardization of eligibility criteria. [Table: see text]
Mucinous adenocarcinoma of the anal canal: Clinical characteristics and outcomes of 767 patients from National Cancer Database.
Authors: Sam Melamed, Jin Sun Lee, Mykola Onyshchenko
Journal: Journal of Clinical Oncology (2022)

3522 Background: Mucinous adenocarcinoma of the anal canal (MAAC) is a relatively rare disease, constituting less than 10% of anal cancers. It carries a relatively poor 5-year survival rate of between 50-60%. MAAC rarity and proximity to rectal mucosa can present a diagnostic challenge as it can be misidentified as adenocarcinoma of the lower rectum. Because of its rarity, the bulk of knowledge of the disease is derived from individual case studies or small institutional reviews. Thus, there remains no clear standard of treatment for AAC. While abdominal perineal resection is the main management approach, the role of systemic therapy and radiation on clinical outcomes remains ill-defined. The lack of national guidelines, variability in institutional approaches and in access to tertiary cancer centers may contribute to differences in patient outcomes and raise the question of healthcare disparities. In this study, we analyzed the data from 767 patients with MAAC from the National Cancer Database (NCDB). Methods: We obtained clinicopathological demographic, socioeconomic data and survival outcomes from 767 patients with MAAC that were registered in the NCDB from 2004 to 2017. The treatment patterns and prognostic factors were analyzed. Results: The majority of patients, 85%, were older than 50. White patients comprised 75.6%, Black 18.8% and Asians 3.3%. Only 3.9% were Hispanics. Among 647 patients who had survival data, the majority received the following therapies: 311 received surgery and chemoradiation, 131 only surgery and 131 only chemoradiation. White and Black patients had similar survival odds, whereas Asian patients had significantly higher overall survival (OS) (HR 0.42). Patients treated at academic facilities had significantly better OS than patients treated at non-academic facilities (HR 1.41-1.57), and patients with private insurance (HR 0.37) had significantly better survival when compared to patients with other insurance types. Patients with only Stage II exhibited significant survival differences when given both surgery and chemoradiation, compared being given either treatment modality alone (HR 0.56); interestingly, male patients in this group did not benefit from adding chemoradiation to surgery while female patients did (p = 0.1, p = 0.011). Conclusions: Surgical resection seems to be the most important treatment modality in MACC, while for patients with stage II addition of chemoradiation statistically significantly improves survival. Access to tertiary cancer centers and therapy costs contribute to differences in survival outcomes, which brings the question of healthcare disparities and the need for national guidelines for MACC management.
Clinical markers of immunotherapy outcomes in sarcoma.
Authors: Marium Husain, David A. Liebner, Hangil Kim, Menglin Xu, James Lin Chen, Gabriel Tinoco
Journal: Journal of Clinical Oncology (2022)

11578 Background: Despite immunotherapy’s promise in oncology, its use for sarcoma remains challenging. There are no sarcoma-specific biomarkers for immune checkpoint inhibitors (ICI). Previously, we reported our institutional experience highlighting ICI activity in 29 patients with sarcoma. In this updated study, we further explore responses to ICI based on ICI regimen and other covariates to identify significant clinical factors in sarcoma outcomes. Methods: Patients in the Ohio State University Sarcoma clinics were enrolled in the Sarcoma Retrospective ICI database from January 1, 2015 through November 1, 2021. Data included treatment regimen (single agent ICI or ICI+combination) along with covariates: stage, age, gender, histology, change in neutrophil-to-lymphocyte ratio (NLR), number of cycles of ICI and immune-related adverse events (irAE). ICI+combination was further categorized into ICI+chemotherapy, ICI+radiation, ICI+surgery or ICI+multiple (more than 2 modalities). Statistical analysis included log rank tests and proportional hazard regression. The primary objective was to evaluate overall survival (OS) and progression-free survival (PFS). Results: One hundred and thirty-five patients met inclusion criteria. We demonstrated improved OS in patients treated with ICI+combination (p = 0.014, median 64 weeks), but no effect on PFS (p = 0.471, median 31 weeks). Whether patients had received single agent or combination ICI, those who received more than 3 cycles of ICI had an improved OS and PFS (p &lt; 0.05 for both). Patients who received single-agent ICI and whose change in NLR was less than 5 had an improved OS (p = 0.002); this was not seen in patients who received ICI+combination therapy (p = 0.441). Patients who had a documented irAE of dermatitis had improved OS but only in the ICI+combination cohort (p = 0.021). There were no differences in OS based on age, gender, histology or sub-categories of ICI+combination. This was not the case for PFS; patients who received any ICI regimen and were younger than 70 had a worse PFS (p = 0.036). Patients who developed an irAE, specifically colitis (p = 0.009), hepatitis (p = 0.048) and dermatitis (p = 0.003) had an improved PFS. There were no differences in PFS based on ICI regimen (or sub-categories of ICI+combination), gender, histology, change in NLR or grade of irAE. Our ICI cohort results are consistent with historical data from our previous study. Further, irAEs are similar to historical data. Conclusions: This retrospective study demonstrates that ICI+combination therapy can improve OS in sarcoma. This is consistent with our prior results of ICI in sarcoma. Benefits in OS/PFS were seen in patients who received more than 3 cycles of ICI and developed certain irAE. These results can direct the optimal duration of ICI therapy. Those with decreased change in NLR also had improved OS, demonstrating a potential prognostic biomarker. Further studies are needed to validate our findings.
Cisplatin (Cis) combined with sintilimab (Sint) and niraparib (Nir) in advanced solid tumors: Updated results.
Authors: TAO Haitao, Lijie Wang, Zhefeng Liu, Jinliang Wang, Guoqing Zhang, Junxun Ma, Yi Hu
Journal: Journal of Clinical Oncology (2022)

2599 Background: PARP inhibitors or chemotherapy combined with PD1/PDL1 inhibitors resulting in enhanced antitumor activity. We previously reported the part 1 result of a phase Ⅰb study exploring the safety and efficacy of Cis plus Sint and Nir. Here we presented the updated survival and safety data. Methods: Eligible pts will receive Sint and Cis on D1, plus Nir on D1-21, every 21-day for up to 4 cycles, following Sint and Nir until disease progression or intolerable toxicity. Part 1 was dose escalation phase followed 3+3 model, and part 2 was dose expansion phase enrolled more patients based on part 1. The primary objective was to determine maximum tolerated dose (MTD)/ recommended part 2 dose (RP2D). Secondary endpoints include objective response rate (ORR) per RECIST v1.1, and safety based on CTCAE v5.0. Results: PR2D of Cis and Nir were 60 mg/m 2 and 100 mg, respectively when combined with sint 200mg. From 7/2019 to 9/2021, 22 pts (13 pts in part2) were enrolled, including 12 small cell lung cancer (SCLC), 7 lung squamous cell carcinoma (LUSC), 2 ovarian cancer (OC) and 1 cervical squamous cell carcinoma (CSCC). Most were male (77.3%, n=17), ECOG=1 (63.6%, n=14), current smoker(68.2%, n=15) and PDL1＜1(50%, n=11). 36.4% (8/22) and 27.3% (6/22) had brain and liver metastasis at baseline, separately. Median follow-up was 6.2 months (range 2.5-10.8). ORR was 27.3% (6/22), DCR was 59.1% (13/22). Median progression-free survival (PFS) was 3.3 months (95%CI 1.9-3.9), and PFS rates at 6 months and 12 months were 28.8% and 10.8%. Median overall survival (OS) was 8.0 months (95%CI 4.9-14.1), 12 months OS rates was 28.5%. Median treatment duration was 4.7 months (range 1.9-15.1). The most common treatment-related adverse events included anemia (90.9%, 20/22, [5 Grade 3/4]), fatigue (77.3%, 17/22, [1 Grade 3/4), γ-glutamyl transpeptidase increased (72.7%, 16/22, [0 Grade 3/4]), leukopenia (68.2%, n=15, [4 Grade 3/4]) and neutropenia (59.1%, n=13, [5 Grade 3/4]). Conclusions: In this updated analysis, Cis combined with Sint and Nir showed clinically meaningful efficacy and an adequate safety profile in previously treated advanced solid tumors. Data need longer follow-up. Clinical trial information: ChiCTR1900024488.